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Kochia scoparia fruit has been used in Asia for a long time. It possesses anti-inflammatory, antiallergic, and antipruritic actions. We investigated the role of a K. scoparia fruit ethanolic extract (KSEE) in allergic airway inflammation in a mouse asthma model. BALB/c mice were sensitized with ovalbumin (OVA) and, upon OVA aerosol challenge, developed airway eosinophilia, mucus hypersecretion, elevations in cytokine, chemokine, and immunoglobulin levels, and upregulation of MMP-9, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) expression. Intragastric administration of KSEE significantly attenuated OVA-induced influx of total leukocytes, eosinophils, neutrophils, macrophages, and lymphocytes into lungs, as well as attenuating levels of interleukin (IL)-4 and IL-5 in a dose-dependent manner. KSEE also significantly reduced the serum levels of total and OVA-specific immunoglobulin (Ig)E and OVA-specific IgG1 release into the airspace. Histological studies showed that KSEE inhibited OVA-induced lung tissue eosinophilia and airway mucus production. Moreover, in whole lung tissue lysates, immunoreactivity showed that KSEE markedly attenuated the OVA-induced increase in expression of ICAM-1, VCAM-1, and MMP-9. These results show that KSEE possesses protective effects against allergic airway inflammation, acts as an MMP-9 inhibitor, and induces a reduction in ICAM-1 and VCAM-1 expression. [ABSTRACT FROM AUTHOR]

Objective: We sought direct evidence that acute exposure to environmental-strength electromagnetic fields (EMFs) could induce somatic reactions (EMF hypersensitivity). Methods: The subject, a female physician self-diagnosed with EMF hypersensitivity, was exposed to an average (over the head) 60-Hz electric field of 300 V/m (comparable with typical environmental-strength EMFs) during controlled provocation and behavioral studies. Results: In a double-blinded EMF provocation procedure specifically designed to minimize unintentional sensory cues, the subject developed temporal pain, headache, muscle twitching, and skipped heartbeats within 100 s after initiation of EMF exposure ( p < .05). The symptoms were caused primarily by field transitions (off-on, on-off) rather than the presence of the field, as assessed by comparing the frequency and severity of the effects of pulsed and continuous fields in relation to sham exposure. The subject had no conscious perception of the field as judged by her inability to report its presence more often than in the sham control. Discussion: The subject demonstrated statistically reliable somatic reactions in response to exposure to subliminal EMFs under conditions that reasonably excluded a causative role for psychological processes. Conclusion: EMF hypersensitivity can occur as a bona fide environmentally inducible neurological syndrome. [ABSTRACT FROM AUTHOR]

Evidence from research and other sources is cited of orgasms elicited by imagery, stimulation of nipple, lips, mouth, anus, rectum, prostate and other body regions, in phantom limbs, during sleep, in response to brain and spinal cord stimulation, during childbirth, modulated by, and in response to, certain drugs and in relation to epileptic seizures. A concept of generalized neurological orgasmic processes involving recruitment, peak excitement and resolution is presented, of which genital orgasm is considered to be a special case. [ABSTRACT FROM PUBLISHER]

Rhinomanometry is a functional test of nasal aerodynamics that measures transnasal airflow and the pressure gradient allowing nasal resistance to be calculated from these data. Three methods of rhinomanometry that are currently in use are anterior rhinomanometry, posterior (peroral) rhinomanometry and postnasal (pernasal) rhinomanometry. The usefulness of this method has increased owing to the development of technology and use of microcomputers connected to the measuring devices. Rhinomanometry can be used for: clinical evaluation of the symptom of nasal obstruction; research in nasal physiology; allergy challenge testing; pre- and post-treatment assessments of surgical or medical therapy; and evaluation of patients with sleep apnea. INSET: Key issues. [ABSTRACT FROM AUTHOR]

Conclusion. Maxillary sinus abnormalities were demonstrated to be associated with maxillary sinus infundibulum narrowing as well as nasal airflow resistance secondary to nonspecific nasal inflammation. Objectives. There is no consensus regarding the pathogenetic roles of allergy and anatomic variations in sinus mucosa abnormalities. We investigated the correlation between allergy and anatomic variations in sinus abnormalities in chronic rhinitis patients in the presence or absence of allergy. Methods: In all, 148 adult patients with allergic rhinitis (AR) and non-allergic rhinitis (NAR) were enrolled. Opacification of sinuses, the size of the maxillary sinus infundibulum, Haller cells, and concha bullosa were evaluated based on computed tomography (CT) images. Simultaneously, nasal airflow resistance was measured. Results: The AR group comprising 105 patients showed maxillary sinus opacification in 45 patients. In the NAR group including 43 patients, soft tissue opacification was observed in 13 patients. There was no significant difference in the incidence of sinus opacification between the AR and NAR groups. Both nasal resistance and the infundibulum size in both the AR and NAR groups with sinus opacification showed significant differences from those without sinus abnormalities. The presence of concha bullosa influenced the sinus opacification in both the AR and NAR groups. [ABSTRACT FROM AUTHOR]

In addition to the effector T-cells subsets, T-cells can also differentiate into cells that play a suppressive or regulatory role in adaptive immune responses. The cell types currently identified as regulatory T-cells (Tregs) include natural or thymic-derived Tregs, T-cells which express Foxp3+CD25+CD4+ and can suppress immune responses to autoreactive T-cells, as well as inducible Tregs, that are generated from naïve T-cells in the periphery after interaction with antigens presented by dendritic cells. Inducible Tregs include TH3 cells, Tr1 cells, and Foxp3+-inducible Tregs. Tregs have been shown to be critical in the maintenance of immune responses and T-cell homeostasis. These cells play an important role in suppressing responses to self-antigens and in controlling inappropriate responses to non-self-antigens, such as commensal bacteria or food in the gut. For example, depletion of CD4+CD25+ Tregs from mice resulted in the development of multi-organ autoimmune diseases. CD4+CD25+ Tregs and/or IL-10-producing Tr1 cells are capable of suppressing or attenuating TH2 responses to allergens. Moreover, adoptive transfer of CD4+CD25+ Tregs from healthy to diseased animals resulted in the prevention or cure of certain autoimmune diseases, and was able to induce transplantation tolerance. Clinical improvement seen after allergen immunotherapy for allergic diseases such as rhinitis and asthma is associated with the induction of IL-10- and TGFβ-producing Tr1 cells as well as FoxP3- expressing IL-10 T-cells, with resulting suppression of the TH2 cytokine milieu. Activation, expansion, or suppression of CD4+CD25+ Tregs in vivo by xenobiotics, including drugs, may therefore represent a relevant mechanism underlying immunotoxicity, including immunosuppression, allergic asthma, and autoimmune diseases. [ABSTRACT FROM AUTHOR]

Following similar events in other European countries, some cases of dermatitis related to contact with China-imported furniture possibly treated with dimethyl(E)-butenedioate (dimethylfumarate [DMF]) were reported to the French institute for public health surveillance at the beginning of September 2008. An active multisource case collection was conducted in order to provide an epidemiological description of this outbreak. Results of this investigation show that, in France, mainly during the 4th quarter of 2008, a large number of people presented dermatological symptoms at least plausibly due to a contact with DMF-treated consumer products. The products involved were mostly shoes and sofa (94% of cases). This work offers an example of a multipartner investigation in the field of environmental health. It also shows how the results obtained contributed to decision-making and resulted in the limitation of DMF-treated products in France and in Europe. [ABSTRACT FROM PUBLISHER]

The immunologic reaction to fungal stimuli has long been thought to be a contributor to the development of sinonasal disease. We aim to review the role of fungi in upper and lower airway inflammatory diseases. The immune response to fungi in the pathogenicity of specific respiratory inflammatory diseases such as allergic bronchopulmonary aspergillosis and a subtype of CRS known as allergic fungal rhinosinusitis has been relatively well described. Fungi are thought to serve both as immunogenic antigens and as adjuncts to inflammation through protease activity. Development of a recent murine mouse model of asthma bypassing the pre-sensitization of allergen further suggests a broader role for fungi in allergic asthma. The literature is lacking in defining a clear presence of fungi within the inflamed sinus cavity of CRS patients and its potential immunologic effects, as well as the utility of antifungal therapy for CRS management. We will review these data and potential common molecular mechanisms activated by fungi in the common pathway toward upper and lower airway inflammatory pathology. [ABSTRACT FROM AUTHOR]

Triggering receptor expressed on myeloid cells-1 (TREM-1) expression is increased during pulmonary fungal infection suggesting that this receptor might be involved in anti-fungal immune responses. To address the role of TREM-1 in a murine model of fungal allergic airway disease, A. fumigatus-sensitized CBA/J mice received by intratracheal injection a mixture of live A. fumigatus conidia and one of a control adenovirus vector (Ad70), an adenovirus containing a gene encoding for the extracellular domain of mouse TREM-1 and the Fc portion of human IgG (AdTREM-1Ig; a soluble inhibitor of TREM-1 function), or an adenovirus containing mouse DAP12 (AdDAP12; DAP12 is an intracellular adaptor protein required for TREM-1 signaling), and examined at various days after challenge. Whole lung TREM-1 levels peaked at day 3 whereas circulating TREM-1 levels peaked at day 30 in this fungal asthma model. AdTREM-1Ig-treated mice exhibited significantly higher airway hyperresponsiveness following methacholine challenge compared with Ad70- and AdDAP12-treated mice. Whole lung analysis of AdTREM-1Ig treated mice revealed markedly higher amounts of fungal material compared with the other groups. ELISA analysis of whole lung and bronchoalveolar lavage samples indicated that several pro-allergic cytokine and chemokines including CCL17 and CCL22 were significantly increased in the AdTREM-1Ig group compared with the other groups. Finally, Pam3Cys and soluble Aspergillus antigens induced TREM-1 transcript expression in macrophages in a TLR2 dependent manner. In conclusion, TREM-1 modulates the immune response directed against A. fumigatus during experimental fungal asthma. [ABSTRACT FROM AUTHOR]

In this study, we investigated the effect of the Meoruh wine (MW), a Korean traditional wine made by the fruits of Vitis amurensis Rupr. (Vitaceae) on the mast cell-mediated allergic inflammation and studied the possible mechanism of action. Mast cell-mediated allergic disease is involved in many diseases such as anaphylaxis, rhinitis, asthma, and atopic dermatitis. MW inhibited compound 48/80-induced systemic anaphylaxis and serum histamine release in a dose-dependent manner in mice. MW decreased immunoglobulin E-mediated local allergic reactions, passive cutaneous anaphylaxis. MW dose-dependently reduced histamine release from human mast cells activated by phorbol 12-myristate 13-acetate and calcium ionophore A23187 (PMACI). The inhibitory effect of MW on histamine release was mediated by suppression of intracellular calcium. In addition, MW attenuated the PMACI-stimulated expression of pro-inflammatory cytokines such as tumor necrosis factor-αα, interleukin-1ββ (IL-1ββ), IL-6, and IL-8 in human mast cells. The inhibitory effect of MW on these pro-inflammatory cytokines was nuclear factor (NF)-κκB dependent. Our findings provide evidence that MW inhibits mast cell-derived allergic inflammatory reactions and involvement of calcium, pro-inflammatory cytokines and NF-κκB in these effects. [ABSTRACT FROM AUTHOR]

Immunosuppressive environmental chemicals may increase the potency of allergens and thereby play a role in the development of allergic diseases. This study''s primary objective was to examine the mechanisms behind the relationship between allergic diseases and the immunosuppression induced by some environmental chemicals. We focused on the modulation of allergic potential in vitro and in mice by the organophosphorus pesticide O, O-diethyl- O-4-nitrophenyl-thiophosphate (parathion) and the organochlorine pesticide 1,1,1-trichloro-2,2-bis(4-methoxy-phenyl)ethane (methoxychlor), with respect to the TH1-type allergen 2,4-dinitrochlorobenzene (DNCB) and the TH2-type allergen trimellitic anhydride (TMA). Mice (4-week-old) were orally administered parathion or methoxychlor. Four weeks after the final dosing, the mice were sensitized to DNCB or TMA, and T-lymphocyte proliferation measured in their (using a local lymph node assay [LLNA]). In addition, we analyzed T-lymphocytes via surface antigen expression and local cytokine production in auricular lymph nodes after treatment with 0.1% DNCB or 0.3% TMA. The estimated concentration of DNCB and TMA to yield a stimulation index (SI) of cell proliferation of three decreased markedly in parathion- and methoxychlor-pre-treated mice. Pesticide pre-treatment induced marked increases in the number of helper and cytotoxic T-cells, levels of TH1 and TH2 cytokines, and gene expression in lymph node cells. According to our results, TH1- and TH2-type allergies are aggravated by prior exposure to immunosuppressive environmental chemicals. [ABSTRACT FROM AUTHOR]

The murine local lymph node assay (LLNA) has been developed as a test method to assess allergic contact dermatitis. In spite of the validity of the LLNA, attention was drawn to the two disadvantages: use of radioactivity for in vivo measurement of lymph node cell proliferation ([3H]-thymidine labeling) and the possibility of false positive results caused by non-specific cell activation as a result of inflammatory processes in the skin (irritation). We aimed to investigate the following non-radioactive endpoints of LLNA: 5-bromo-2′′-deoxyuridine (BrdU) incorporation ex vivo and in vivo, in vivo and ex vivo cytokine production with or without phytohemagglutinin (PHA) stimulation. Here, 8-12-week-old female BALB/c mice were treated topically with the strong sensitizer 2,4-dinitrochlorobenzene (DNCB) in acetone:olive oil (AOO, 4:1 [v/v]) at levels of 0.025, 0.05, 0.01, or 0.25% (w/v). Ear thickness was also measured to determine the differentiation index (DI) indicating the proportion of non-specific activation due to irritating properties of test compound. At the concentration of 0.05%, stimulation index (SI) value was found to be 3 for DNCB based on in vivo and ex vivo BrdU incorporation. The results of the in vivo and ex vivo non-radioactive LLNA assays were compatible both with each other and with previous radioactive LLNA data. Our results indicate that non-radioactive endpoints may be used as an alternative to the [3H]-thymidine LLNA. The levels of TH1 cytokines (IL-2 and IFNγγ) and TH2 cytokines (IL-4 and IL-5) in lymph node cell cultures were significantly ( P < 0.01) increased when DNCB was applied at the concentrations of 0.05 and 0.1%, respectively. As the DI was > 1, the applied concentrations of DNCB caused only allergic effect but not any irritant effect. This study reports that the use of these non-radioactive endpoints can assess allergic contact dermatitis caused by chemicals. [ABSTRACT FROM AUTHOR]

Purpose: NC/Tnd mice, a spontaneous model for human atopic dermatitis, are also useful animal models for various corneal disorders accompanying allergic diseases. The purposes of the current study were to investigate the development of retinal degeneration in NC/Tnd mice. Materials and Methods: Histological examination was performed to determine time-dependent alterations of the retina in NC/Tnd from 8 to 28 days of age. Apoptotic cells were determined by TUNEL assay. Retinal function was examined by electroretinography. Fundoscopy was performed in NC/Tnd mice at 8 weeks of age. Melanin contents in whole-eye extracts were measured by spectrophotometry. Since the retinal degeneration 1 ( rd1) mutation in the rod photoreceptor cyclic guanosine monophosphate phosphodiesterase 6 ββ-subunit ( Pde6b rd1) has been identified in laboratory mice, the possible existence of the rd1 mutation was analyzed with PCR genotyping and gene sequencing. C57BL/6, WB, and C3H/HeN mice were used as controls. Results: Histological examination revealed rapid postnatal retinal degeneration in NC/Tnd mice. The number of apoptotic cells in the outer nuclear layer (ONL) increased with aging, and finally the ONL disappeared. Histological abnormality was not obvious in the inner nuclear layer or the ganglion cell layer. Electroretinography shows no response in adult NC/Tnd mice. Fundoscopic observation revealed hypopigmentation in the retina, and melanin contents in the eye were significantly reduced when compared with other inbred strains. Insertion in the rd1 allele was confirmed and a nonsense mutation of Pde6b rd1 gene was determined in NC/Tnd mice. Conclusions: NC/Tnd mice also preserve the Pde6b rd1 gene mutation resulting in the rapid postnatal retinal degeneration similar to that in C3H/HeN mice. Unlike C3H/HeN mice, since melanin contents of the retina in NC/Tnd mice was decreased, unknown defects may be present in the process of melanin composition in retinal pigment epithelial cells during fetal development of NC/Tnd mice. [ABSTRACT FROM AUTHOR]

CD4++ T helper (Th) cells act as important regulators of the mammalian adaptive immune response. CD4++ Th cells were originally characterized as either Th1 or Th2 types, based on the cytokines they produce. Over the past two decades, however, we have attained a much more detailed understanding of CD4++ T-cell differentiation, functions, and gene expression profiles, which led to the identification of additional types, such as the Th17 and induced regulatory T cells. Recently, researchers have characterized yet another novel and distinct population that exists among these immune-modulatory cells. The ''Th9'' cells were first identified as a Th2 subpopulation that produced exceptionally large quantities of the Th2-specific cytokine interleukin 9. However, experimental analysis revealed that Th9 cells had divergent regulatory capabilities and were critically involved in different immune processes. In particular, we now know that Th9 acts as a major contributor to the onset and progression of allergies, especially asthma. Here, we will review the heterogeneity and biology of CD4++ Th cells and summarize the characteristics known to date of interleukin 9 and Th9 cells to build a framework for better understanding of their roles in disease processes, especially in allergy-induced asthma. [ABSTRACT FROM AUTHOR]

Fecal calprotectin seems to provide a safe and non-invasive means of helping differentiate between patients with organic and non-organic intestinal disease. Aim of our study was to evaluate if FC levels at birth and at first month of age can be a predictive biomarker of organic or functional gastrointestinal disease (FGIDs) and/or allergic disease diagnosed in 2 years old children. Between December 2007 and January 2008 a telephonic interview has been proposed to the parents of 109 consecutive healthy children, in which FC was measured at birth two years before. For our study, a modified version of the original paediatric questionnaire on paediatric functional gastrointestinal disorders (QPGS) was used for the interview. Specific questions were added to detect allergic diseases. We didâ ™™nt find any statistically significant result between FC measured at birth and during first month of life in children with allergy or not. The interference of familiarity does not lead to a statistically significant change in the fecal calprotectin values during the first month of life. [ABSTRACT FROM AUTHOR]

Carbamazepine (CBZ) is a useful anticonvulsive drug associated with rare severe adverse drug reactions. The physio-pathological mechanisms of these reactions are unknown although evidence of immunological activation has been reported. The ability of 9-acridinecarboxaldehyde, a CBZ metabolite, to interact with leukocyte constituents was demonstrated, and catabolism of this compound into acridine (AI) and acridone (AO) was observed in vitro. In this study, we have assessed ex vivo the role of the extra-hepatic 9-acridinecarboxaldehyde pathway in the metabolism of CBZ. First, we verified the presence of the terminal metabolites AI and AO in CBZ-treated patients. Then, we tested ex vivo the transformation of CBZ, epoxy CBZ, iminostilbene, and AI into AO in the blood of these patients. We observed no direct formation of hydroxylated CBZ metabolites in isolated blood, and CBZ did not react with blood cells. Conversely, we detected a dose-dependent transformation of epoxy CBZ, iminostilbene, and AI into AO with individual variations from patient to patient. AO might thus be considered as a metabolite of 9-acridinecarboxaldehyde that does not react with cells (detoxicant pathway) as well as a marker of the formation of toxic AI derivatives (toxicant pathway). [ABSTRACT FROM AUTHOR]

While pharmaceutical companies provide abundant health and medical information on their Web sites, little is known about consumers' perceptions of pharmaceutical companies as a health information source and the impact of pharmaceutical Web sites on health-related attitudes and behaviors. Findings from this study suggest that a pharmaceutical company can be perceived to be just as credible as a government health agency, and that Web site interactivity and consumer involvement with online health information affect the persuasive effects of the pharmaceutical company's message. Implications for future research and for the role of pharmaceutical companies in health communication are discussed. [ABSTRACT FROM AUTHOR]

Objectives. To investigate the relationship between air-borne allergen exposure and Voice Handicap Index scores in patients seeking medical treatment for rhinitis. Methods. As we had previously identified a higher-than-expected incidence of allergy in patients presenting to a voice clinic, we undertook a prospective audit of patients without specific voice-related complaints presenting to a rhinology clinic to see if these patients might have unrecognized vocal dysfunction. To this end 70 consecutive patients with no pre-reported voice-related symptoms presenting to a teaching hospital rhinology clinic underwent skin prick testing to common air-borne allergens and completed the Voice Handicap Index (VHI) questionnaire. Discriminant performances in the Voice Handicap Index and its individual domains and questions were determined using analysis of variance. An allergy-specific subset of the VHI was constructed and tested using receiver operating characteristic (ROC) statistics. Results. There were 30 males and 40 females. Mean age was 36 ± 12 years. Dust mite (83%), house dust mite (55%), and grass pollen (40%) were the commonest allergens, and 23 patients did not react to common allergens. Mean VHI score was 23.7 ± 20.1 in patients with ≥4 allergens, 10.8 ± 21.3 in patients with fewer than 4 allergies, and 7.8 ± 8.5 in non-allergics ( P = 0.044; analysis of variance). Nine VHI questions best discriminated between allergic and non-allergic patients ( P < 0.05), and the combined VHI-9 score had a ROC area under the curve of 0.85. Conclusions. Patients with more air-borne allergies have a higher incidence of undiagnosed vocal dysfunction, as determined by the raised Voice Handicap Index score, than those with fewer or no such allergies. As noted, earlier work has shown that, conversely, patients with vocal dysfunction have a high incidence of undiagnosed allergy. [ABSTRACT FROM AUTHOR]

The realization, that the immune system can be the target of many chemicals including environmental contaminants and drugs with potentially adverse effects on the host's health, has raised serious concerns within the public and the regulatory agencies. At present, assessment of immunotoxic effects relies on different animal models and several assays have been proposed to characterize immunosuppression and sensitization. The use of whole animals, however, presents many secondary issues, such as expense, ethical concerns, and eventual relevance to risk assessment for humans. Furthermore, due to the new policy on chemicals (REACH), in the European Union, in vitro methods will play a major role in the near future. In addition, there is still a lack of human cell-based immunotoxicity assays for predicting the toxicity of xenobiotics toward the immune system in a simple, fast, economical, and reliable way. Hypersensitivity and immunosuppression, for which animal models have been developed and validated, are considered the primary focus for developing in vitro methods in immunotoxicology. Nevertheless, in vitro assays, as well as in vivo models, to detect immunostimulation and autoimmunity are also needed. Even if no validated alternative in vitro tests to assess immunotoxicity exist, in the last decade, much progress has been made toward these assays. Such models can be, at least, used for the pre-screening and hazard identification of unintended immunosuppression and contact hypersensitivity of direct immunotoxicants. Following a brief introduction to immunotoxicology and to in vivo models use to assess immunotoxicity, this manuscript will review the state-of-the-art in the field of in vitro immunotoxicity. [ABSTRACT FROM AUTHOR]

Temporary henna-based tattoos, particularly popular among western tourists holidaying in exotic places, can expose to the risk to develop allergic reactions. Although hypersensitivity to henna is extremely rare, para-phenylenediamine, which is sometimes added to henna to obtain a dark, blackish color, is a frequent contact sensitizer. The purpose of this article is to review the literature about allergic reactions to temporary henna tattoos and outline the causes, clinical aspects and complications of this practice that should not be regarded as innocuous and risk-free. [ABSTRACT FROM AUTHOR]

Using Medline, Embase, and the Science Citation Index, we summarize the cutaneous adverse effects of transdermal and parenteral fentanyl. The fentanyl transdermal therapeutic system (TTS; patch) provides continuous systemic delivery of fentanyl ( N-phenyl- N-(1-(2-phenylethyl)-4-piperidinyl) propanamide), a potent opioid analgesic, for 72 hours. Clinical studies of fentanyl TTSs demonstrated varying rates of irritation at the application site, ranging from none to 42%, with a median of 25%. Most descriptions of skin reactions included erythema at the application site, indicating irritant dermatitis. Skin testing in 2 subjects receiving parenteral doses concluded that although immunoglobulin E (IgE) antibodies to fentanyl exist, few cases of immediate-type allergic reactions to fentanyl have been substantiated. Comparing the reactions to anesthetic agents during allergenic testing demonstrated positive 'wheal and flare' to fentanyl in only 1 of 50 patients (2%). Pruritus has been frequently reported during administration of epidural fentanyl, but allergenicity has not been shown. The few case reports of possible anaphylactic reactions to fentanyl have not clearly demonstrated fentanyl as the causal agent. In addition, transdermal and intravenous/epidural routes of administration may not be comparable because of large differences in plasma concentrations: When these results are taken together, fentanyl (TTS) has shown limited skin intolerance. [ABSTRACT FROM AUTHOR]

Dopamine D2 receptors exist in both low- and high-affinity states (D2High), the latter being the functionally relevant state. Cocaine self-administration produces an increase in D2High, a phenomenon that could explain why cocaine administration results in hypersensitivity to dopamine, even though drug addicts were found to have a decreased number of striatal dopamine D2 receptors. As nicotine acts through the same mesocortical dopaminergic signaling pathways as other stimulant drugs, which are known to increase the levels of D2High, we hypothesized that nicotine exposure could produce an increase in D2High levels. We determined D2High levels in rats after nicotine administration (1.5 mg/kg/day; 14 days), in rats voluntarily self-administering nicotine using an intravenous self-administration (IVSA) protocol (mean dose 0.5 mg/kg/day; 14 days), as well as after a prolonged withdrawal. An increase in the levels of D2High was found in rats who had nicotine administered at a uniform dose, as well as in rats who self-administered nicotine via IVSA, but these changes appear to normalize over time, as indicated by lower D2High levels in rats after a prolonged withdrawal period. We suggest that nicotine-induced elevation in D2High levels could be participating in hypersensitivity to dopamine following nicotine exposure. [ABSTRACT FROM AUTHOR]

Background. Against the background of an increasing prevalence of allergies, the epidemiology of asthma in relation to age is still a matter of debate. To further clarify the prevalence of asthma, asthmatic symptoms, and their change over time within a population sample, we analyzed longitudinal data from the Study of Health in Pomerania (SHIP). Methods. Standardized questionnaires for asthma and asthmatic symptoms were available in 4310 individuals aged 20-75 years. The population sample underwent a 5-year follow-up with 3300 subjects reexamined. The questionnaire evaluated estimates to describe the prevalence in wheeze, chest tightness, shortness of breath, coughing, nocturnal symptoms, and asthma attacks in the past 12 months, current medications, current asthma, and nasal allergies at baseline and its longitudinal net change. Results. The prevalence of current asthma at the baseline study was 1.8% [95% confidence interval (CI 1.4-2.2)], those of nasal allergies 16.7% (95% CI 15.6-17.9). Sixteen percent of asthmatic individuals were not medically treated. The net changes in asthmatic symptoms per 60 months of follow-up ranged between a decrease by 2.0% (chest tightness at night) and an increase by 1.2% (nocturnal attack of coughing). The proportions of subjects with current asthma remained unchanged. The prevalence of current asthma and symptoms was higher in young individuals, whereas the net change over time was slightly increasing at the age of 36 and above. Conclusion. Despite the fact of a high prevalence of subjects complaining of nasal allergies, the overall prevalence of current asthma remained low over time. The prevalence in asthma and asthmatic symptoms as well as its net changes over 5 years were age dependent. [ABSTRACT FROM AUTHOR]

Background. The ability to assess adequate reductions in immunoglobulin E (IgE) in allergic bronchopulmonary aspergillosis (ABPA) has been a concern with regards to omalizumab treatment. Objective. To describe the clinical course and serial measured IgE levels in two adult patients with elevated IgE levels, hypersensitivity to Aspergillus fumigatus, and bilateral bronchiectasis who were treated with omalizumab. Clinical Descriptions. Patient 1 met commonly used critieria for ABPA and had a more than 3-fold increase (from 702 to 2462 IU/ml) in measured IgE 4 months after starting omalizumab. Two years after starting omalizumab, the IgE level decreased to baseline (473 IU/ml) even when corticosteroids were discontinued. Patient 2 had near normalization of elevated IgE levels when treated with corticosteroids but IgE levels subsequently rose again to over 10,000 IU/ml. After reducing the IgE level to 586 IU/ml with higher corticosteroid doses, omalizumab was initiated. Twenty months after starting omalizumab, the measured IgE was 510 IU/ml. Based on published omalizumab treatment-associated total/free IgE ratios, the estimated free IgE levels for both patients after more than a year of omalizumab treatment was less than their pre-omalizumab treatment IgE levels. Conclusions. These data suggest that omalizumab can be beneficial in treating ABPA and that measured IgE levels can still be useful in this context. Noting the pattern of IgE levels associated with ABPA exacerbations and with corticosteroid treatment may help both with achieving an IgE level appropriate for omalizumab treatment and with the interpretation of measured IgE changes associated with omalizumab treatment. [ABSTRACT FROM AUTHOR]

The immune response is a tightly regulated process, which normally results in protection from infection and tolerance of innocuous environmental antigens. However, in allergic disease, the activated immune response results in a chronic pro-inflammatory state characterized by antibody secretion (IgE) and T cell activation to normally well-tolerated antigens. Currently, the treatment of allergic disease is focused on the suppression of key inflammatory mediators or inflammatory cell populations and include anti-histamines, anti-leukotrienes, β2 adrenergic receptor agonists and corticosteroids. However, these approaches only provide a temporary suppression of disease symptoms. Successful long-term treatment can only be provided by allergen-specific immunotherapy (allergen-SIT), which restores normal immunity against allergens. This review will discuss novel approaches to the management of allergy and asthma by targeting the T regulatory cell via modulation of the commensal microbiota and allergen-SIT. [ABSTRACT FROM AUTHOR]

Background. Exposure to indoor allergens is an established risk factor for poor asthma control. Current guidelines recommend removing pets from the home of patients with asthma. Objectives. This cross-sectional study was conducted to determine the prevalence of furry pet ownership in asthmatics compared to nonasthmatics and to identify factors associated with furry pet ownership among those with asthma. Secondary analysis assessed characteristics among asthmatics that might be associated with allowing a furry pet into the bedroom. Methods. Using data from The National Asthma Survey collected from 2003 to 2004, we carried out univariate and multiple regression analyses, in 2009, to identify independent predictors of furry pet ownership in asthma sufferers after controlling for potential confounders. Results. Overall, asthmatics were more likely to own a furry pet than nonasthmatic individuals in the general population (49.9% versus 44.8%, p < .001). Multivariate analysis showed that female sex, older age, white race, and high income were independent predictors of furry pet ownership among asthmatics. Additionally, 68.7% of patients with asthma who own a furry pet allowed them into their bedroom. Higher income and carrying out ≤2 environmental control practices in the home were associated with increased likelihood of allowing a furry pet into the bedroom. Conclusions. Furry pet ownership is equally or more common among asthmatics compared to those without asthma. The majority of asthmatics with furry pets allow them into the bedroom. Recognizing and addressing these problems may help decrease asthma morbidity. [ABSTRACT FROM AUTHOR]

Background. Obesity and asthma prevalence have both risen among children over the last several decades, and research efforts increasingly suggest that obesity is associated with asthma. Some, but not all, studies have shown that the effect of obesity on asthma is stronger among nonatopic individuals than among those with atopy. Systemic inflammation may be a factor in this relationship. Objective. To examine the association of obesity with atopic and nonatopic asthma among U.S. children and to assess the role of C-reactive protein. Design. Nationally representative data from the National Health and Nutrition Examination Survey (NHANES) were used to examine the relationship of weight to current asthma using logistic regression. Overweight was defined as ≥85th percentile of body mass index (BMI)-for-age and obesity was defined as ≥95th percentile of BMI-for-age. The presence of at least one positive allergen-specific immunoglobulin E (IgE) was used to stratify the relationship by atopic status in 2005–2006 data ( n = 3387). Setting and Participants. Stratified, multistage probability sampling was used to identify survey participants. This analysis includes children ages 2–19 ( n = 16,074) from the 1999–2006 NHANES who have information on BMI and current asthma. Main Outcome Measure. Self-report of doctor-diagnosed current asthma. Results. Obesity was significantly related to current asthma among children and adolescents (odds ratio [OR]: 1.68, 95% confidence interval [CI]: 1.33, 2.12). The association was stronger in nonatopic children (OR: 2.46, 95% CI: 1.21, 5.02) than in atopic children (OR: 1.34, 95% CI: 0.70, 2.57) (interaction p value = .09). C-reactive protein levels were associated with current asthma in nonatopic children, but not after adjusting for BMI. Conclusion. Excess weight in children is associated with higher rates of asthma, especially asthma that is not accompanied by allergic disease. [ABSTRACT FROM AUTHOR]

Bare-metal stents were a significant advance over percutaneous transluminal coronary angioplasty in the treatment of atherosclerotic coronary artery disease. However, bare-metal stents are plagued by a restenosis rate of approximately 30%. First-generation drug-eluting stents greatly reduce restenosis but are associated with a troublesome persistence of late thrombotic events. Stent thrombosis is a devastating clinical event, with high mortality rates. While the superior efficacy of drug-eluting stents is unquestioned, the relative safety of bare-metal and drug-eluting stents has been hotly debated. This article will address the safety of bare-metal and drug-eluting stents, and will describe current and future stent systems that promise to maintain current efficacy, while reducing thrombosis risk even further. INSETS: Definitions of stent thrombosis.;Stent thrombosis risk factors.;Academic research consortium definitions of stent thrombosis.;Key issues [ABSTRACT FROM AUTHOR]

Leuprolide (Lupron) is a synthetic analog of naturally occurring gonadotropin-releasing hormone (GnRH). Leuprolide is used as a hormonal antagonist in the treatment of advanced prostatic cancer, and as hormonal therapy in the treatment of endometriosis. Off-label, it is also used in premenopausal or perimenopausal women with hormone-responsive breast cancer for the purpose of ovarian ablation. Ever since its FDA approval in 1985, many adverse reactions have been reported in association with leuprolide ranging from local skin irritation to severe anaphylactoid reactions. In this case report, we present a case of hypersensitivity vasculitis (serum sickness) in a patient who received leuprolide for his prostate cancer. Serum sickness has never been reported as a side-effect of leuprolide. Our case is the first case of serum sickness associated with leuprolide. We emphasize that physicians using leuprolide should be wary of signs and symptoms of hypersensitivity vasculitis or serum sickness. [ABSTRACT FROM AUTHOR]

Background and aim: Corydalis heterocarpa is a biennial herb in South Korea, with spikes of yellow flowers. It has been used for as a folk medicine to cure travail and spasm. However, studies on this herb and its secondary metabolites have rarely been reported. In the present study, we isolated secondary metabolite libanlibanoridin from Corydalis heterocarpa. We have also examined the effect of libanoridin on the inflammatory cytokines production in phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore, A2318 stimulated human mast cell line, HMC-1. PMA plus A23187 significantly increased interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor (TNF)-α production compared to media control (P < 0.05). Results: We report that treatment with libanlibanoridin can inhibit PMA plus A23187-induced IL-1β, IL-6, IL-8, and TNF-α production in a concentration-dependent manner with IC50 of 0.002, 1.38, 1.48, and 0.36 μg/ml, respectively. Maximal inhibition rates of IL-1β, IL-6, IL-8, and TNF-α production by libanlibanoridin were about 117.5%, 86.22%, 86.41%, and 90.74%, respectively. libanoridin inhibits the mRNA expression of IL-1β, IL-6, IL-8, and TNF-α. libanoridin also inhibits the expression of cyclooxygenase-2. Conclusion: These results indicate that libanlibanoridin may be helpful in regulating mast cell-mediated allergic inflammatory response. [ABSTRACT FROM AUTHOR]

To determine how estrogen exacerbates allergies, the effects of 17β-estradiol (E2) on lymphocyte proliferation were investigated. BALB/c mice were ovariectomized, administered 3.2 μg E2, and sensitized with 50 μL 4-ethoxymethylene-2-phenyl-2-oxazolin-5-one. After 7 days, their spleens were excised and flow cytometrically analyzed. The CD8+CD45RA−CCR7− cell–to–CD8+ cell ratio in the spleen was greater in the E2-administered mice than in the controls. Splenocytes were cultured under concanavalin A stimulation, with or without E2. After 4 days, the above ratio was greater in the case of E2-treated splenocytes. E2 increases the number of effector memory CD8+ lymphocytes during sensitization in contact hypersensitivity. [ABSTRACT FROM AUTHOR]

IgE-mediated allergic diseases (e.g., allergic rhinoconjunctivitis, atopic asthma and food allergy) are prevalent (up to 30%) in the general population and are increasing in developed countries. In infants and young children, non-IgE-mediated food allergy is also prevalent. In addition to easily recognized organ-specific symptoms, allergic diseases can cause neuropsychiatric symptoms, such as irritability and hyperactivity, in otherwise healthy individuals. This is also likely to occur in children with autism spectrum disorder (ASD). Moreover, the discomfort and pain associated with allergic diseases could aggravate behavioral symptoms in ASD children. Allergic conditions are easily treatable; however, ASD children may be underdiagnosed and/or undertreated for allergic and other common childhood diseases, in part due to their impaired communication skills. Practicing physicians should be aware of the potential impact of allergic diseases on behavioral symptoms and cognitive activity in ASD children. However, they also need to be aware that certain symptoms often attributed to 'allergy' by caregivers may not be immune mediated and should understand that behavioral symptoms can also be affected by many non-IgE-mediated causes. INSET: Key issues. [ABSTRACT FROM AUTHOR]

Decorative tattooing involves the introduction of exogenous pigments and/or dyes into the dermis to produce a permanent design. Practiced for thousands of years, it has gained tremendous popularity during the past 20 years, especially among the young. Tattoo-associated cutaneous complications have only been reported since the end of the 19th Century. With the increased prevalence of tattooed individuals, dermatologists have witnessed increasing numbers of patients presenting with complaints about their tattoos. Complications primarily include infections, hypersensitivity reaction to tattoo pigments, benign and sometimes malignant tumors arising on tattoos, and the localization of various dermatoses to tattoos. INSETS: Acute and chronic infections occurring on tattoos;Tattoo-hypersensitivity reactions;Benign and malignant tumors occurring on tattoos;Miscellaneous cutaneous complications related to tattooing [ABSTRACT FROM AUTHOR]

Objectives. Voice problems affect up to 30% of the population at some time during their life, and in particular it affects those who use their voice professionally. Patients who commonly present with dysphonia are often found to have symptoms of both allergy and reflux. Clinical examination of the larynx often makes it difficult to differentiate between the main causative factors of dysphonia, as the clinical findings on nasendoscopy between reflux and allergy are similar. Laryngopharyngeal reflux (LPR), an entity of gastro-oesophageal reflux, is a common diagnosis made in the voice out-patient clinic. Few studies have been able to successfully correlate management of LPR and outcome of dysphonia. Allergy or more specifically allergic rhinitis is said to affect approximately 24% of the population, but few studies have investigated its role in dysphonia. Design. Prospective observational study. Settings. University teaching hospital otolaryngology department. Participants. Fifteen new patients with primary voice disorder were investigated for possible LPR and allergy from April 2007 to October 2007. All patients were tested using the validated reflux symptom index (RSI), reflux finding score (RFS) to diagnose LPR, and both skin prick tests (SPT) and nasal nitric oxide (NO) levels to diagnose the presence of allergy. Main outcome measures. Prevalence of symptoms of reflux and allergy in patients presenting with primary voice disorders, and also whether dysphonia thought to be caused by LPR could actually be due to allergy. Results. No positive correlation or statistical significance was found between reflux and allergy. From our sample 20% (three patients) were diagnosed with LPR and 67% (ten patients) with allergy. The three patients diagnosed with LPR also had concomitant allergy. Conclusions. In our patient cohort, three times as many patients demonstrated allergy compared with LPR. This has led us to question if some patients with allergic laryngitis are being misdiagnosed with LPR and thereby being over-treated with proton pump inhibitors (PPIs). [ABSTRACT FROM AUTHOR]

Aims: To explore parental experiences of caring for a child with medically diagnosed severe food allergies (MDSFA) in New Zealand. Method: This study employed a qualitative methodology, interpretive descriptive analysis, and involved interviews with four parents of children with MDSFA from two different regions in New Zealand. Results: The analysis of the interviews revealed that the experience of parenting a child with MDSFA is an experience of feeling unsupported in the effort to keep the child healthy and safe. Three major themes emerge from this study: the experience of isolation, the burden of accessing resources, and the cost of living with MDSFA. Conclusion: The general lack of support experienced by these families from health care professionals is a significant concern both for primary and tertiary health care providers. Multi-disciplinary support is required for these families, and currently there is a lack of health care professionals with the knowledge to support these families. This research highlights that there is a significant need for both workforce development and further research in the area of MDSFA in New Zealand. [ABSTRACT FROM AUTHOR]

Evidence suggests that the predisposition towards atopy begins early in life. Maternal allergy has been associated with an increased risk of the development of allergic disease in offspring. Some studies suggest that the development of childhood atopy may also be influenced by prenatal allergen exposure. In this study, a respiratory allergen exposure model was used to determine the impact of maternal sensitization (with or without additional exposures during pregnancy) on subsequent pup responses to homologous or heterologous allergen. Female BALB/c mice received two intratracheal aspiration (IA) exposures to Metarhizium anisopliae crude antigen (MACA) or Hank’s buffered salt solution (HBSS) prior to breeding. Some mice also received three additional exposures during pregnancy. Control mothers did not receive treatment. Young adult offspring received three IA exposures to MACA, house dust mite extract (HDM) or HBSS. Offspring sensitized as young adults to either HDM or MACA developed an airway inflammatory response, including increased bronchoalveolar lavage fluid lactate dehydrogenase activity, total protein and total and differential cell counts compared to offspring exposed to HBSS. Increased airway responsiveness to methacholine was observed in pups treated with HDM but not with MACA. Maternal sensitization status (with or without gestational allergen exposure) had no effect on offspring response to either MACA or HDM. In conclusion, this study demonstrates that IA administration of MACA or HDM extract to young adult BALB/c mice induces the development of an inflammatory airway response. In contrast to previous reports, neither maternal sensitization nor gestational allergen exposure could be demonstrated to have a clear effect on offspring sensitization. This discrepancy may be a function of the respiratory sensitization and exposure protocol used in this study, which mimics natural sensitization more closely than do parenteral routes of exposure. [ABSTRACT FROM AUTHOR]

Objective. Painful symptoms are prevalent in patients with eosinophilic oesophagitis but experimental data are sparse. The aim of this study was to compare the pain response to experimental oesophageal stimulation in 14 patients with eosinophilic oesophagitis and 15 healthy volunteers. Material and methods. A multimodal probe was placed in the oesophagus. The participants were subjected to mechanical, thermal and electrical pain stimuli followed by perfusion with 0.1 M HCl. Pain scores, referred pain areas and evoked brain potentials to electrical stimulation of the oesophagus were recorded. Results. Patients tolerated significantly less acid perfused in the oesophagus (median 123 versus 200 ml; P = 0.02) and felt the burning sensation evoked by the acid earlier (median 2.0 versus 5.0 min; P = 0.01). Eight patients had coexisting gastro-oesophageal reflux disease. Six patients had pure eosinophilic oesophagitis, and this group felt the acid earlier than those with concomitant reflux or the healthy volunteers (median 0.8 versus 2.0 and 5.0 min; P = 0.03). There were no differences between patients and controls in the responses to mechanical or thermal stimulation ( P > 0.4). Furthermore, no differences were found for the proxies of central nervous system sensitization (response to electrical stimulations, referred pain areas or evoked brain potentials; P > 0.1). Conclusions. Patients with eosinophilic oesophagitis are hypersensitive to acid perfused in the oesophagus, and pathophysiologic findings are likely confined to the peripheral tissue. Reflux from physiological acid may play a role in the symptoms of eosinophilic oesophagitis. [ABSTRACT FROM AUTHOR]

Introduction. Scombroid syndrome (histamine fish poisoning – HFP) is a complex of symptoms caused by biogenic amines, mainly histamine, contained in seafood. The diagnosis of HFP is quite difficult as the symptoms of this particular condition are similar to the symptoms of a normal allergic syndrome. Materials and methods. We have collected 10 cases (3 male and 7 female) of HFP and 50 non-HFP patients (35 female and 15 male) with allergic disorders, all from the Emergency Department of Ospedale Civile Maggiore in Verona. Results. As expected, tryptase serum concentrations of most of the patients with allergic or anaphylactic disorders were increased above normal value (24.4 ± 8.0 ng/mL mean ± SD, normal value <11 ng/mL), whereas the tryptase serum concentrations of all the 10 patients with HFP were within the normal range (8.1 ± 1.8 ng/mL). Discussion. Our data suggest that tryptase serum concentrations can discriminate between the allergic and HFP syndromes. As the tryptase half-life is 90–120 min, blood samples must be taken 1–2 h from the beginning of symptoms. Conclusions. Finding a biomarker could help physicians to formulate a correct diagnosis and thus in choosing the best therapeutic strategy. In this work, we analyzed the role of tryptase serum concentrations to differentiate real allergic syndromes from the HFP syndrome, which causes similar histamine-mediated effects by a different mechanism. [ABSTRACT FROM AUTHOR]

There is wide variability in the epidemiology and management of childhood asthma and related atopic diseases globally. Urbanized, affluent Western countries tend to have a higher prevalence of these diseases compared with Asian nations. However, recent studies have shown that the prevalence in Asia is increasing, although the rate of increase has slowed in the more developed Asian cities. Some possible causes for these differences are socioeconomic status, degree of urbanization, rates of infection, healthcare practices and genetic factors. Importantly, there are significant differences in the way asthma and allergic diseases are managed within Asia. This is of great concern because of the health implications, as these diseases are some of the most common chronic conditions that affect both adults and children. This review compares the differences in prevalence and management between Asia and the West, and discusses some of the possible reasons behind these variations. INSET: Key issues. [ABSTRACT FROM AUTHOR]

Irritant-induced inflammation of the airways may aggravate respiratory allergy induced by chemical respiratory allergens. Therefore, it was studied whether airway irritation by sulfur dioxide (SO2) would enhance respiratory allergic reactions to trimellitic anhydride (TMA), using a rat model. Brown Norway (BN) rats were topically sensitized, subsequently exposed for a single time or repeatedly to 300 ppm SO2, and challenged by inhalation to a distinctly irritating or minimally irritating concentration of TMA after the (last) SO2 exposure. Repeated exposure to SO2 alone reduced breathing frequency during exposure, and caused epithelial alterations including hyperplasia and squamous metaplasia, and infiltration of polymorphonuclear inflammatory cells into nasal tissues, larynx, trachea, and bronchi/bronchioli. Histopathological changes were less prominent after 1 day of SO2 exposure. Repeated pre-exposure to SO2 reduced the number of TMA-induced apnoeas, in an SO2 exposure duration-dependent manner. This effect of SO2 on TMA-induced functional allergic reactions (apnoeas) was distinct only when the TMA challenge concentration was not too irritating itself. Repeated pre-exposure to SO2 reduced TMA-induced laryngeal ulceration, goblet-cell hyperplasia, and inflammation in the lungs in most animals, regardless of the TMA challenge concentration. The SO2-induced replacement of normal respiratory epithelium by less sensitive, squamous epithelium may offer an explanation for the, unexpected, reduced allergic manifestation. However in a few animals, SO2 appeared to facilitate TMA-induced irritation, probably due to incomplete protection. Overall, SO2 exposure of TMA-sensitized rats reduced TMA-related allergic respiratory responses in most animals. [ABSTRACT FROM AUTHOR]

Saliva eosinophil cationic protein (ECP) is higher in asthmatic adults than in healthy ones. However, its relationship with asthma severity, other atopic conditions and allergic sensitization have not been reported. Saliva collection is painless, readily acceptable to children and parents, and can be a potentially useful body fluid to measure asthma biomarkers. We recruited 102 physician-diagnosed young asthmatic subjects from outpatient clinics with change in FEV1≥12% with inhaled salbutamol and collected data on asthma severity, concurrent allergic rhinitis (AR) and atopic dermatitis (AD), and medication used (bronchodilator and corticosteroid). We measured whole saliva and serum ECP and performed skin prick tests (SPT) for three dust mites ( Dermatophagoides pteronyssisinus, Dermatophagoides farinae and Blomia tropicalis) and two cockroaches ( Periplaneta americana and Blatella germanica). Median salivary ECP was 84.6 μg/l (inter-quartile range [IQR]: 40.9–147.9) and median serum ECP was 14.7 μg/l (IQR: 6.4–32.1). Serum ECP was only higher in children whose sleep was disturbed by asthma in the past year than those who were not (geometric mean [GM]: 18.9 vs. 11.1 μg/l, relative mean difference [RMD]: 1.71 [95%CI: 1.09–2.69]). Serum ECP was increased among asthmatic children on inhaled corticosteroid than those not using them (GM: 15.6 vs. 8.1 μg/l, RMD: 1.93 [95%CI: 1.11–3.39]). Salivary ECP was not associated with asthma severity, concurrence of atopic conditions, medications used, or any SPT parameter. Saliva ECP did not correlate with serum ECP (rs = 0.032, p = 0.790). Salivary and serum ECP did not correlate with wheal size for any skin prick test. [ABSTRACT FROM AUTHOR]

Metals are commonly used in cosmetic products for blocking ultraviolet light or coloring pigments; however, some metals exceed specific concentrations and can cause serious safety issues such as skin troubles and allergies. It is, therefore, important to measure the exact amount of metal in cosmetic products. However, the exact concentrations of metals in cosmetics that contain many organic and inorganic materials like oils, polymers, waxes, polyols, surfactants, and metallic powders are difficult to analyze due to the matrix effect. In this study, we developed and optimized a method to characterize six different metals (Iron, Copper, Zinc, Lead, Nickel and Cadmium) in cosmetics by using Flame Atomic Absorption Spectroscopy (FAAS). Commercial products in liquid and powder phase were prepared for analysis and spiking solutions were added to the analyte. The method was developed by optimizing acid for decomposition, acid ratio, and sample weight. The recoveries for accuracy test ranged from 92-105% and the linearity correlation coefficients were no less than 0.99. The relative standard deviations (% RSD) for repeatability were between 0.5-2.0%. In addition, robustness and ruggedness test results showed consistent quality of data under different conditions. Consequently, the proposed method is a rapid and simple protocol to determine metals in liquid and powder type of cosmetics with a high confidence level. [ABSTRACT FROM AUTHOR]

Exposure to diesel exhaust particulate matter (DEP) exacerbates asthma. Likewise, similar effects have been reported with exposure to the oxidizing air pollutant ozone (O3). Since levels of both pollutants in ambient air tend to be simultaneously elevated, we investigated the possible synergistic effect of these agents on the exacerbation of allergic airways disease in mice. Male BALB/c mice were sensitized ip with ovalbumin (Ova) or vehicle only, then exposed once per week for 4 wk via nose-only inhalation (4 h) to the PM2.5 fraction of DEP (2 mg/m3), O3 (0.5 ppm), DEP and O3, or filtered air, and then challenged with aerosolized ovalbumin. Ova sensitization in air-exposed mice enhanced pulmonary inflammatory cell infiltration, several indicators of injury in the lung (lactate dehydrogenase, albumin and total protein), and lung resistance (RL) and elastance (EL) in response to methacholine (MCh) aerosol challenge. DEP exposure did not enhance the Ova-induced increase in pulmonary cell infiltration, indicators of injury, or RL and EL. O3 exposure enhanced the Ova-induced increase in inflammatory cell infiltration and N-acetylglucosaminidase (NAG) in the lung, but had no effect on RL or EL. DEP co-exposure significantly attenuated the O3-induced increase in cell infiltration and indicators of injury; co-exposure had no effect on EL relative to air-exposed Ova-sensitized mice. However, only DEP-O3 co-exposure significantly increased the Ova-induced increase in RL. Thus, O3 and DEP co-exposure exacerbated airways hyperresponsiveness, a response that was not associated with parallel increases in pulmonary inflammation and one that may be mediated by a unique mechanism. [ABSTRACT FROM AUTHOR]

Objective. Malabsorption of low-digestible carbohydrates is physiological, but poorly tolerated in some patients. We investigated symptom anticipation and microbial fermentation as possible mechanisms of carbohydrate intolerance in patients with self-reported food hypersensitivity. Material and methods. In a randomized, double-blind, cross-over study, 27 consecutive patients with unexplained, self-reported food hypersensitivity were given 10 g lactulose and 10 g glucose (placebo). Symptoms and pulmonary excretion of hydrogen and methane were assessed. Short-chain fatty acids (SCFAs), lactate and prostaglandin E2 (PGE2) were analyzed in rectal dialysis fluid, and compared to dialysates from nine healthy volunteers. Results. Post-lactulose symptom scores were correlated with habitual symptom scores ( r = 0.6, p = 0.001), significantly higher than post-glucose symptom scores ( p = 0.01) and significantly higher in patients than controls ( p = 0.0007). Levels of SCFAs, lactate and PGE2 in rectal dialysates were not significantly different after lactulose and glucose, or between patients and controls. Hydrogen excretion was not correlated with symptom scores. Conclusions. The findings suggest that self-reported food hypersensitivity is related to microbial fermentation of malabsorbed carbohydrates and not to symptom anticipation solely. Levels of SCFAs, lactate and PGE2 in rectal dialysates could not explain the fermentation-associated hypersensitivity. [ABSTRACT FROM AUTHOR]

Visual loss associated with allergic fungal sinusitis (AFS) is uncommon, with incidence estimates ranging from 1.46% to 3.7%. Uncertainty remains concerning the pathophysiology of visual loss in the setting of AFS. Proposed theories include direct or indirect compression of the optic nerve or orbital inflammatory changes causing an optic neuritis. A case of precipitous visual loss in an adult male with clinical and radiographic evidence of optic neuropathy is reported. After surgical and medical interventions this patient showed improvement in optic nerve function. Visual loss associated with AFS is a rare but potentially devastating condition. [ABSTRACT FROM AUTHOR]

Basophils are relatively rare leukocytes that potentially play a role in both systemic anaphylaxis and, owing to their ability to migrate from the blood into various other tissues, in more localized aspects of allergic inflammation. Given their greater sensitivities to allergen provocation compared with their tissue-fixed mast cell counterparts, and by virtue of their capacity to more readily generate Th2-type cytokines, basophils have been considered to play more than a bystander role in initiating and maintaining allergic disorders. However, only very recently has clearer evidence shed light on the abilities of this cell type to orchestrate chronic allergic inflammation and promote Th2 immunity in the early induction stages of allergy. This review summarizes these recent advances in understanding the role of basophils in orchestrating and maintaining allergic responses. INSET: Key issues. [ABSTRACT FROM AUTHOR]

The T-helper 2 (TH2) bias associated with pregnancy may predispose the pregnant mother to the development or exacerbation of allergic disease. To determine the effects of pregnancy on pre-existing maternal sensitization, we sensitized BALB/c mice before breeding by two intratracheal aspiration (IA) exposures to the fungal allergen, Metarhizium anisopliae crude antigen (MACA). Some mice also received three IA exposures to MACA on gestational days 11, 15, and 19. After weaning, all mice were challenged IA with MACA before killing. To determine the effects of pregnancy on susceptibility to future sensitization, naïve parous and nulliparous BALB/c mice were sensitized by three IA exposures to MACA or to Hank’s buffered salt solution vehicle control. Pregnancy did not have a significant effect on individual inflammatory parameters (airway responsiveness to methacholine, total serum and bronchoalveolar lavage fluid (BALF) IgE, BALF total protein, lactate dehydrogenase activity, and total and differential cell counts) following allergen challenge in sensitized mice, regardless of post-breeding allergen exposure. In conclusion there was a weak inhibition of the overall response in mice exposed to allergen during pregnancy compared to identically treated nulliparous mice. In contrast, parous mice that did not encounter allergen post-breeding tended to have exacerbated responses. Parity had no significant impact on future susceptibility to sensitization. [ABSTRACT FROM AUTHOR]

Rationale. Previous studies have demonstrated associations of high ozone levels with increased epidemiologic as well as lung function measures of asthma activity. Objectives. In an observational study during the summer months, we hypothesized that higher ambient ozone levels are associated with more frequent symptoms, higher airway and systemic inflammation, as well as worse lung function in asthmatics as compared with non-asthmatic individuals. Methods. Thirty-eight asthmatics and thirteen healthy control subjects residing in metropolitan Atlanta were enrolled during peak ozone season. Medical histories, quality-of-life questionnaires, spirometry, serum immunoglobulin (IgE), peripheral eosinophil counts, and exhaled nitric oxide (NO) were obtained during study visits. Personal ozone exposures over the 2 days before presentation were estimated based on location and activity surveys. Main results. Upper airway symptoms were more frequent in asthmatics. Higher levels of ozone were associated with worse airflow obstruction, lower quality of life scores, greater eosinophilia, and higher exhaled NO levels in asthmatics. Finally, both asthmatics and non-asthmatics with allergies showed associations between air quality and airway inflammation. Conclusions: In adults with asthma but not controls studied during peak ozone season, increasing ozone exposure predicted lower lung function and increased biomarkers of respiratory and systemic inflammation. These associations were enhanced in atopic participants, both with and without asthma. Importantly, the study findings were noted while atmospheric ozone levels were predominantly within the current and revised national air quality standards. [ABSTRACT FROM AUTHOR]

1. The cytochrome P450-mediated metabolism of the tea tree oil ingredient p-cymene (p-isopropyltoluene) was studied by the application of in vitro enzymatic assays using different recombinant human cytochrome P450 enzymes. 2. In total, four enzymatic products were identified by gas chromatography-mass spectrometry. The enzymatic products identified were: thymol (2-isopropyl-5-methylphenol), p-isopropylbenzyl alcohol, p,α,α-trimethylbenzyl alcohol, and p-isopropylbenzaldehyde. 3. The enzymatic products of p-cymene resulted from catalysed enzymatic arene-epoxidation and hydroxylation reactions by the studied cytochrome P450 enzymes.4. An in vivo study could only confirm the formation of one enzymatic product, namely thymol. Thymol was identified after enzymatic hydrolysis of glucuronide and sulphate conjugates in collected blood and urine samples. 5. The obtained results may help to increase the understanding of cases where skin sensitization and irritation by tea tree oil-containing products that are involved with allergic reactions of users of these products. The results also indicate that skin sensitization and irritation reactions not only can be explained by the frequently in literature reported auto-oxidation of tea tree resulting in bioactive oxidized products, but also now by the formation of epoxide intermediates resulting from catalysed arene-epoxidation reactions by selected human cytochrome P450 enzymes which are also located in different organs in humans. [ABSTRACT FROM AUTHOR]

In this chapter, we introduce the concepts and methodologies of population analysis as applied to analyzing pharmacokinetic and pharmacodynamic data. One of the key determining characteristics of the population approach is that through it, one seeks not only to characterize deterministic trends in the data, but also to identify and estimate the magnitudes of the important sources of variability within the data. The first section of this chapter provides an introduction to the primary concepts of, and motivation for, population modeling by way of a hypothetical case study. Then, the various methodologies that have been employed throughout the history of population analysis are described in further detail. Of these, the most commonly employed today is nonlinear mixed-effects (NLME) modeling. Finally, notable examples of the application of population PK and PK/PD modeling to treatments for allergies and asthma are discussed. Population PK models have frequently been used to extrapolate exposures to special populations, such as pediatrics, as well as to optimize treatment regimens and trial designs for these populations. Population PK/PD models have most frequently been applied to analyzing and interpreting data from wheal and flare trials, but are also becoming increasingly important in the analysis of PD data from monoclonal antibodies. [ABSTRACT FROM AUTHOR]